TY - JOUR

T1 - Coagulation factors and natural anticoagulants in polycythemia vera patients, relation with JAK2V617F mutation load

AU - Korsakova, N

AU - Silina, N

AU - Efremova, E

AU - Fominykh, M

AU - Polushkina, L

AU - Martynkevich, I

AU - Kobilyanskaya, V

AU - Golovina, O

AU - Shuvaev, V

AU - Voloshin, S

AU - Papayan, L

PY - 2019

Y1 - 2019

N2 - Background : Thrombotic complications are among the most common causes of morbidity and mortality in myeloproliferative neoplasms, including polycythemia vera (PV). 95% PV patients share JAK2V617F mutation, that is associated with increased thrombotic risk. The role of platelet and leukocyte activation, accounting for coagulation activation in PV, is well established, while data on hemostatic abnormalities in PV, and their relationship with JAK2V617F burden is contradictory. Aims : To evaluate the hemostatic parameters in PV patients, predisposing high thrombosis risk, and their relation with JAK2V617F allele burden. Methods : The study included 27 PV patients. JAK2V617F mutation presence and allele burden were determined using allele specific polymerase-chain reaction. Coagulation assays (factors V, VIII, von Willebrand, antithrombin, protein C activities, fibrinogen concentration, von Willebrand factor antigen and free protein S level) were performed by standard techniques. The control group consisted of 68 healthy persons. STATISTICA 6.0 was used. Median and 95% confidence interval (CI) were calculated. Mann-Whitney and Spearman rank tests were applied, the differences considered statistically significant with p<0,05. Results : All but 3 PV patients in the study were JAK2V617F-positive, and 1 had mutation in JAK2-gene 12 exon. The age median constituted 55,5 years (95%CI 27,5-70,8). JAK2V617F allele burden data was available in 15 PV patients with median 15,6% (95%CI 4,5-34,0). The results of hemostatic parameters and JAK2V617F allele burden correlations are shown in Tables 1 and 2 respectively. Conclusions : The coagulation factor VIII increase and natural anticoagulants PC and PS decrease alongside with high fibrinogen in PV patients confirm the hypercoagulability, while VWF:Ag increase suggests the endothelium damage and dysfunction that can further enhance prothrombotic state in PV. The correlation analysis revealed a direct relationship between JAK2V617F allele burden and such procoagulants as FVIII and VWF (both activity and, especially, antigen) that contributes to the higher incidence of thrombosis depending on JAK2V617F burden. (Table Presented) .

AB - Background : Thrombotic complications are among the most common causes of morbidity and mortality in myeloproliferative neoplasms, including polycythemia vera (PV). 95% PV patients share JAK2V617F mutation, that is associated with increased thrombotic risk. The role of platelet and leukocyte activation, accounting for coagulation activation in PV, is well established, while data on hemostatic abnormalities in PV, and their relationship with JAK2V617F burden is contradictory. Aims : To evaluate the hemostatic parameters in PV patients, predisposing high thrombosis risk, and their relation with JAK2V617F allele burden. Methods : The study included 27 PV patients. JAK2V617F mutation presence and allele burden were determined using allele specific polymerase-chain reaction. Coagulation assays (factors V, VIII, von Willebrand, antithrombin, protein C activities, fibrinogen concentration, von Willebrand factor antigen and free protein S level) were performed by standard techniques. The control group consisted of 68 healthy persons. STATISTICA 6.0 was used. Median and 95% confidence interval (CI) were calculated. Mann-Whitney and Spearman rank tests were applied, the differences considered statistically significant with p<0,05. Results : All but 3 PV patients in the study were JAK2V617F-positive, and 1 had mutation in JAK2-gene 12 exon. The age median constituted 55,5 years (95%CI 27,5-70,8). JAK2V617F allele burden data was available in 15 PV patients with median 15,6% (95%CI 4,5-34,0). The results of hemostatic parameters and JAK2V617F allele burden correlations are shown in Tables 1 and 2 respectively. Conclusions : The coagulation factor VIII increase and natural anticoagulants PC and PS decrease alongside with high fibrinogen in PV patients confirm the hypercoagulability, while VWF:Ag increase suggests the endothelium damage and dysfunction that can further enhance prothrombotic state in PV. The correlation analysis revealed a direct relationship between JAK2V617F allele burden and such procoagulants as FVIII and VWF (both activity and, especially, antigen) that contributes to the higher incidence of thrombosis depending on JAK2V617F burden. (Table Presented) .

KW - Janus kinase 2

KW - adult

KW - antigen

KW - antithrombin

KW - blood clotting factor 8

KW - complication

KW - conference abstract

KW - congenital malformation

KW - controlled study

KW - correlation analysis

KW - endogenous compound

KW - endothelium lesion

KW - enzyme activity

KW - female

KW - fibrinogen

KW - gene expression

KW - gene frequency

KW - gene mutation

KW - genetic association

KW - genetic susceptibility

KW - human

KW - hypercoagulability

KW - leukocyte activation

KW - major clinical study

KW - male

KW - morbidity

KW - mortality

KW - mutational load

KW - myeloproliferative neoplasm

KW - polycythemia vera

KW - procoagulant

KW - protein C

KW - protein S

KW - protein expression

KW - protein function

KW - thrombocyte activation

KW - thrombosis

KW - von Willebrand disease

KW - von Willebrand factor

UR - https://www.mendeley.com/catalogue/781d2f5b-a6d7-3358-8cf0-40a4f7ecd667/

U2 - 10.1002/rth2.12229

DO - 10.1002/rth2.12229

M3 - статья в журнале по материалам конференции

VL - 3

SP - 703

EP - 704

JO - Research and Practice in Thrombosis and Haemostasis

JF - Research and Practice in Thrombosis and Haemostasis

SN - 2475-0379

IS - S1

ER -